{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:46:37Z","timestamp":1791585997593,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T00:00:00Z","timestamp":1611792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M650574"],"award-info":[{"award-number":["2019M650574"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8177021278"],"award-info":[{"award-number":["8177021278"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pulmonary arterial hypertension (PAH) is a common complication of congenital heart disease (CHD). Deubiquitinase cylindromatosis (CYLD) has been reported to significantly aggravate vascular smooth muscle cell (VSMC) phenotypic transformation, proliferation, and migration. Here, we aimed to further investigate its roles and underlying mechanisms in the CHD\u2010PAH development. The expression of CYLD in the lung tissues from CHD\u2010PAH patients and monocrotaline (MCT) plus aortocaval (AV)\u2010induced PAH rats, pulmonary artery smooth muscle cells (PASMCs) from MCT\u2010AV\u2010induced PAH rats, and human PASMCs (HPASMCs) was evaluated. After infection with CYLD siRNA or pcNDA3.1\u2010CYLD, the proliferation, migration, and apoptosis of HPASMCs were measured using an EdU assay, transwell and scratch wound healing assays, and flow cytometric assay, respectively. An adeno\u2010associated virus (AAV) vector encoding CYLD was used to suppress CYLD expression by being intratracheally instilled in rats 7 days before MCT\u2010AV treatment. The results showed that CYLD was increased in the lung tissues from CHD\u2010PAH patients and MCT\u2010AV\u2010induced PAH rats, and in PASMCs from MCT\u2010AV\u2010induced PAH rats. The contractile\u2010type HPASMCs expressed low levels of CYLD, while the proliferative synthetic\u2010type HPASMCs expressed high levels of CYLD. In addition, CYLD could mediate HPASMC dysfunction, which regulated HPASMC phenotypic transformation and proliferation via the modulation of p38 and ERK activation, while CYLD regulated HPASMC migration via the modulation of p38 activation. In vivo results demonstrated that the local suppression of CYLD expression could attenuate the increased levels of PAH and its associated pulmonary vascular remodeling in MCT\u2010AV\u2010induced PAH rats. Collectively, these results indicated that CYLD might be a potential novel therapeutic target for the prevention of PAH and pulmonary vascular remodeling in CHD\u2010PAH through the modulation of HPASMC dysfunction.<\/jats:p>","DOI":"10.1002\/jcp.30298","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T01:04:28Z","timestamp":1611882268000},"page":"6297-6311","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["CYLD mediates human pulmonary artery smooth muscle cell dysfunction in congenital heart disease\u2010associated pulmonary arterial hypertension"],"prefix":"10.1002","volume":"236","author":[{"given":"Jing\u2010jing","family":"Zhou","sequence":"first","affiliation":[{"name":"Center of Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology Guangdong Cardiovascular Institute Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Li","sequence":"additional","affiliation":[{"name":"The Animal Experimental Centre, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010he","family":"Wang","sequence":"additional","affiliation":[{"name":"The Animal Experimental Centre, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian\u2010min","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0521-895X","authenticated-orcid":false,"given":"Jian\u2010guo","family":"He","sequence":"additional","affiliation":[{"name":"Center of Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,1,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2006.08.016"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201607-1515PP"},{"issue":"2","key":"e_1_2_10_4_1","first-page":"389","article-title":"Pulmonary artery adventitial changes and venous involvement in primary pulmonary hypertension","volume":"146","author":"Chazova I.","year":"1995","journal-title":"American Journal of Pathology"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssynbio.8b00126"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-10-248526"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.09.014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.18.4.533"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070318"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10528-013-9616-7"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2010.02.017"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01802"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2010.02.003"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019613"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1067\/mtc.2002.121497"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.02.118"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.117.007249"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00614"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/eht072"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2013.01.018"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062694"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1315"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-175489"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201201-0164OC"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1053\/sarh.2002.31550"},{"issue":"16","key":"e_1_2_10_26_1","first-page":"1091","article-title":"[Screening study of pulmonary arterial hypertension in patients with congenital heart diseases]","volume":"92","author":"Sun Y. J.","year":"2012","journal-title":"Zhonghua Yi Xue Za Zhi"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070312"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214697"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.632208"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1177\/2045894018788267"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(19)38415-6"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00319.2003"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20190304"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.102036"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2011.04.031"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509526200"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309859"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2016.05.71"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2020.09.005"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30298","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.30298","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30298","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T23:26:06Z","timestamp":1693005966000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.30298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,28]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/jcp.30298"],"URL":"https:\/\/doi.org\/10.1002\/jcp.30298","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,28]]},"assertion":[{"value":"2020-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}